研究概要
这些研究共同凸显了在扩增的 T 细胞疗法中保留 NK 细胞群体的价值,并提示固有免疫细胞联合免疫治疗对神经母细胞瘤具有协同作用。
中文摘要
T淋巴细胞是一类新兴的细胞免疫疗法,临床前研究显示其有望用于癌症治疗,尤其是神经母细胞瘤。γδ T细胞具有类似先天免疫的特性,可不依赖主要组织相容性复合体(MHC)识别而天然杀伤肿瘤细胞,因此可采用健康供者来源的异基因T细胞疗法。目前的一个局限是,不同个体的白细胞采集物在T细胞扩增能力上差异显著。克服这一问题有助于充分发挥异基因T细胞疗法的潜力。本研究分析了健康成年供者来源的T细胞扩增情况,发现唑来膦酸和IL-2刺激时,具有较强效应活性的自然杀伤(NK)淋巴细胞也会随T细胞一同扩增。NK细胞的存在与T细胞扩增潜力及T细胞疗法的总体效力均相关。然而,细胞疗法与抗体类免疫治疗药物地努图昔单抗联用时,其效力似乎不受T/NK细胞含量影响,无论体外还是体内实验均如此;这减轻了个体间扩增差异对疗效的影响。总体而言,这些研究凸显了在扩增的T细胞疗法中保留NK细胞群的价值,并提示联合先天免疫细胞疗法可能对神经母细胞瘤产生协同作用。
展开英文摘要原文
T lymphocytes represent an emerging class of cellular immunotherapy with preclinical promise to treat cancer, notably neuroblastoma. The innate-like immune cell subset demonstrates inherent cytoxicity toward tumor cells independent of MHC recognition, enabling allogeneic administration of healthy donor-derived T cell therapies. A current limitation is the substantial interindividual T cell expansion variation among leukocyte collections. Overcoming this limitation will enable realization of the full potential of allogeneic T-based cellular therapy. Here, we characterize T cell expansions from healthy adult donors and observe that highly potent natural killer (NK) lymphocytes expand with T cells under zoledronate and IL-2 stimulation. The presence of NK cells correlates with both the expansion potential of T cells and the overall potency of the T cell therapy. However, the potency of the cell therapy in combination with an antibody-based immunotherapeutic, dinutuximab, appears to be independent of T/NK cell content both in vitro and in vivo , which minimizes the implication of interindividual expansion differences toward efficacy. Collectively, these studies highlight the utility of maintaining the NK cell population within expanded T cell therapies and suggest a synergistic action of combined innate cell immunotherapy toward neuroblastoma.
论文信息
- 作者
- Jonus HC、Burnham RE、Ho A、Pilgrim AA、Shim J、Doering CB、Spencer HT、Goldsmith KC
- 单位
- Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Oncoimmunology2022